This is a renewal application for a program project grant designed to elucidate important aspects of development in intact and experimentally damaged mammalian basal ganglia and cerebral cortex. The research follows two main themes: The first is development of neuronal communication and conditioned learning in the cortex and basal ganglia. The second theme concerns the effects on neuronal communication of prenatal and early postnatal brain damage. Each of the five component projects of this grant is addressed to at least one of these themes and to their underlying hypotheses. The research involves basic electrophysiological, pharmacological, and morphological studies of developing neurons in vitro (brain slices) and in vivo. Important behavioral studies will assess recovery of function after prenatal cortical lesions, and will examine the cellular bases of conditioned learning. Many of the experiments to be undertaken are designed as models for developmental brain disabilities, including mental retardation. Some of the basic approaches are already being applied to immature human brain tissue in a clinical program on pediatric epilepsy (separately funded). Finally, this program project grant acts as an important training vehicle for graduate and postdoctoral students in the Mental Retardation Research Center.